De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

Abstract Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30...

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Autores principales:	Akira Nishi, Shusuke Numata, Atsushi Tajima, Xiaolei Zhu, Koki Ito, Atsushi Saito, Yusuke Kato, Makoto Kinoshita, Shinji Shimodera, Shinji Ono, Shinichiro Ochi, Akira Imamura, Naohiro Kurotaki, Shu-ichi Ueno, Nakao Iwata, Kiyoshi Fukui, Issei Imoto, Atsushi Kamiya, Tetsuro Ohmori
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2f03255fb4a14d7c9a0b4184ac4e7df3
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spelling	oai:doaj.org-article:2f03255fb4a14d7c9a0b4184ac4e7df32021-12-02T11:40:22ZDe novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity10.1038/s41598-017-02792-z2045-2322https://doaj.org/article/2f03255fb4a14d7c9a0b4184ac4e7df32017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02792-zhttps://doaj.org/toc/2045-2322Abstract Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.Akira NishiShusuke NumataAtsushi TajimaXiaolei ZhuKoki ItoAtsushi SaitoYusuke KatoMakoto KinoshitaShinji ShimoderaShinji OnoShinichiro OchiAkira ImamuraNaohiro KurotakiShu-ichi UenoNakao IwataKiyoshi FukuiIssei ImotoAtsushi KamiyaTetsuro OhmoriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Akira Nishi Shusuke Numata Atsushi Tajima Xiaolei Zhu Koki Ito Atsushi Saito Yusuke Kato Makoto Kinoshita Shinji Shimodera Shinji Ono Shinichiro Ochi Akira Imamura Naohiro Kurotaki Shu-ichi Ueno Nakao Iwata Kiyoshi Fukui Issei Imoto Atsushi Kamiya Tetsuro Ohmori De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
description	Abstract Here we report de novo non-synonymous single-nucleotide variants (SNVs) by conducting whole exome sequencing of 18 trios consisting of Japanese patients with sporadic schizophrenia and their parents. Among nine SNVs, we explored the functional impact of the de novo mutation in TBL1XR1 [c.30 C > G (p.Phe10Leu)], a gene previously found to be associated with autism spectrum disorder and epilepsy. Protein structural analysis revealed that Phe10Leu mutation may decrease the structural stability of the TBL1XR1 protein. We demonstrate that Phe10Leu mutation alters the interaction of TBL1XR1 with N-CoR and β-catenin, which play critical roles in regulation of Wnt-mediated transcriptional activity. Consistently, TBL1XR1-mediated activation of Wnt signaling was up-regulated by Phe10Leu mutation. These results suggest that a de novo TBL1XR1 point mutation could alter Wnt/β-catenin signaling activity. Further studies are required to clarify the involvement of TBL1XR1 mutations in neuropsychiatric conditions.
format	article
author	Akira Nishi Shusuke Numata Atsushi Tajima Xiaolei Zhu Koki Ito Atsushi Saito Yusuke Kato Makoto Kinoshita Shinji Shimodera Shinji Ono Shinichiro Ochi Akira Imamura Naohiro Kurotaki Shu-ichi Ueno Nakao Iwata Kiyoshi Fukui Issei Imoto Atsushi Kamiya Tetsuro Ohmori
author_facet	Akira Nishi Shusuke Numata Atsushi Tajima Xiaolei Zhu Koki Ito Atsushi Saito Yusuke Kato Makoto Kinoshita Shinji Shimodera Shinji Ono Shinichiro Ochi Akira Imamura Naohiro Kurotaki Shu-ichi Ueno Nakao Iwata Kiyoshi Fukui Issei Imoto Atsushi Kamiya Tetsuro Ohmori
author_sort	Akira Nishi
title	De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
title_short	De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
title_full	De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
title_fullStr	De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
title_full_unstemmed	De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity
title_sort	de novo non-synonymous tbl1xr1 mutation alters wnt signaling activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2f03255fb4a14d7c9a0b4184ac4e7df3
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De novo non-synonymous TBL1XR1 mutation alters Wnt signaling activity

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